Capegard

Capegard - (fluoropyrimidine carbamate) with anti-tumor activity
Capegard is a prodrug of 5’-deoxy-5-fluorouridine (5’-DFUR) which is changed to 5 fluoro uracil.
Capegard is generally administered orally.
Capegard is also have anti-metabolite activity

Capecitabine

Capegard

500mg

Cipla

Capegard indication

Colorectal cancer
Adjuvant treatment in Duke’s colon cancer
First line therapy in colon-rectal cancer metastasis
Breast cancer
In metastatic breast cancer: used in combination with docetaxel after failure of anthracycline containing chemotherapy

Mechanism of action

Capecitabine is a prodrug, it is metabolizing to 5-FU. In both non-cancer and cancer cells, 5-FU is metabolized in to 5-fluoro-2-deoxyuridine monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP)
These two metabolites cause injury to the tumor cells by two major ways
FdUMP and the folate cofactor (N5-10-methylenetetrahydrofolate), which binds to thymidylate synthase (TS) to form covalently bound ternary complex.

This binding prohibits the production of thymidylate from 2’-deaxyuridylate
Thymidylate an important messenger of thymidylate triphosphate.
It is essential for DNA synthesis; therefore, insufficiency of this compound leads to inhibit cell division
Nuclear transcriptional enzymes can falsely inserted FUTP alternative to uridine triphosphate during RNA synthesis. This metabolic failure can hinder with RNA conversion and protein synthesis via assembly of counterfeit RNA

Capecitabine is largely metabolized to 5-FU enzymatically. In liver, 60 kDa carboxylesterase hydrolyses to 5’-deoxy-5-fluorocytidine.
Cytidine deaminase is an enzyme which converts 5’-DFCR to 5’-DFUR. Thymidine phosphorylase is also an enzyme which involved in the conversion of 5’-DFUR to 5-FU active drug

Monotherapy

First line therapy of patients with advanced colorectal cancer

The usual dose of Capegard is 1250mg/m2 should be taken orally as twice daily (morning and evening dose 2500mg/m2); therapy continue for 2 weeks followed by 1-week rest period given as 3 weeks cycle

Adjuvant therapy for Duke’s colon cancer

The usual dose of Capegard is 1250mg/m2 orally as twice daily (morning and evening dose 2500mg/m2); for 2 weeks followed by 1 week given as 3 weeks for total 8 cycles (24 weeks)

Breast cancer

Monotherapy:
Recommended dose: 1250mg/m2 should be taken as orally for twice daily
In combination with docetaxel;
1250mg/m2 of Capegard with 75mg/m2 of docetaxel for 3 weeks
Capegard should be administered within 30 minutes after a meal

In pediatric

The safety and efficacy of the Capegard tablets in pediatric patients has not been established

Leucovorin: the toxicity and concentration of 5-FU increased by Leucovorin. In elderly patients, phenytoin and Leucovorin is administered weekly which may cause; diarrhea, dehydration, enterocolitis which may causes death.

CYP2C9 substrate: other than warfarin, there is no drug interaction occurs while concomitant with CYP2C9 substrates

Drug-food interaction:
In case of administering Capegard with food, it leads to reduce the rate and duration of absorption of Capegard.
Capegard tablets should be administered within 30 minutes after food

Contraindications

Capegard is contraindicated to renal impairment patients

Capegard is contraindicated in patients with hypersensitivity to Capegard or other components

If patient fail to take the dose of Capegard , must consult with medical oncologist and follow the suggestions
Do not self-medicate.
The missed dose must be skipped and follow the regular dosing schedule
Do not double the dose

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